Predicting abiraterone efficacy in advanced prostate cancer: Insights from marker of proliferation Ki67.

BACKGROUND: KI67 is a well-known biomarker reflecting cell proliferation. We aim to elucidate the predictive role of KI67 in the efficacy of abiraterone for patients with advanced prostate cancer (PCa). METHODS: Clinicopathological data of 152 men with metastatic PCa, who received abiraterone therapy were retrospectively collected. The KI67 positivity was examined by immunohistochemistry using the prostate biopsy specimen. The predictive value of KI67 on the therapeutic efficacy of abiraterone was explored using Kaplan-Meier curve and Cox regression analysis. The endpoints included prostate-specific antigen (PSA) progression-free survival (PSA-PFS), radiographic PFS (rPFS), and overall survival (OS). RESULTS: In total, 85/152 (55.9%) and 67/152 (44.1%) cases, respectively, received abiraterone at metastatic hormone-sensitive (mHSPC) and castration-resistant PCa (mCRPC) stage. The median KI67 positivity was 20% (interquartile range: 10%-30%). Overall, KI67 rate was not correlated with PSA response. Notably, an elevated KI67-positive rate strongly correlated with unfavorable abiraterone efficacy, with KI67 ≥ 30% and KI67 ≥ 20% identified as the optimal cutoffs for prognosis differentiation in mHSPC (median PSA-PFS: 11.43 Mo vs. 26.43 Mo, p < 0.001; median rPFS: 16.63 Mo vs. 31.90 Mo, p = 0.003; median OS: 21.77 Mo vs. not reach, p = 0.005) and mCRPC (median PSA-PFS: 7.17 Mo vs. 12.20 Mo, p = 0.029; median rPFS: 11.67 Mo vs. 16.47 Mo, p = 0.012; median OS: 21.67 Mo vs. not reach, p = 0.073) patients, respectively. Multivariate analysis supported the independent predictive value of KI67 on abiraterone efficacy. In subgroup analysis, an elevated KI67 expression was consistently associated with unfavorable outcomes in the majority of subgroups. Furthermore, data from another cohort of 79 PCa patients with RNA information showed that those with KI67 RNA levels above the median had a significantly shorter OS than those below the median (17.71 vs. 30.72 Mo, p = 0.035). CONCLUSIONS: This study highlights KI67 positivity in prostate biopsy as a strong predictor of abiraterone efficacy in advanced PCa. These insights will assist clinicians in anticipating clinical outcomes and refining treatment decisions for PCa patients.

Reliability and repeatability of 2021 ARCO classification and its guiding significance in treatment of nontraumatic osteonecrosis of the femoral head.

BACKGROUND: The study was designed to evaluate the interobserver reliability and intraobserver repeatability of the 2021 Association Research Circulation Osseous (ARCO) classification and explore its guiding significance in the treatment of nontraumatic osteonecrosis of the femoral head (ONFH). METHODS: In this retrospective study, we randomly selected and investigated 50 sets of preoperative computed tomography or magnetic resonance imaging scans from 96 patients (139 hips) to validate the reliability and repeatability of the 2021 ARCO classification. Patients with a nano-hydroxyapatite/polyamide-66 support rod were included in the clinical efficacy study. The Harris hip score (HHS) was used to assess hip function. Femoral head collapse of > 2 mm was considered radiological failure. Total hip arthroplasty (THA) was performed for clinical failure, and follow-up was discontinued. RESULTS: The average kappa value of interobserver consistency was 0.652. The average rate of consistency was 90.25%, and the average kappa value of intraobserver consistency was 0.836. Eighty-two patients (122 hips) were enrolled and followed up for a mean of 43.57 ± 9.64 months. There was no significant difference in the HHS among the three groups before surgery, but the difference was statistically significant at the last follow-up. Among them, types 1 and 2 had significantly higher scores at the last follow-up than preoperatively (P < 0.05), whereas type 3 had a lower score at the last follow-up than preoperatively, although the difference was not statistically significant (P > 0.05).According to the imaging evaluation, the failure rate of type 1, 2, and 3 at the last follow-up was 0%, 19%, and 87%, respectively. Univariate analysis showed that the femoral head survival rate of radiography was significantly affected by the new classification system (P = 0.00). At the last follow-up, the incidence rate of THA in type 1, 2, and 3 was 5%, 7%, and 31%, respectively. Univariate analysis showed that the femoral head survival rate was significantly affected by the new classification system (P = 0.001). CONCLUSIONS: The 2021 ARCO classification for early-stage ONFH shows substantial consistency and repeatability. We do not recommend femoral head-preserving surgery for patients with type 3 ONFH.

Advances on Hormones in Cosmetics: Illegal Addition Status, Sample Preparation, and Detection Technology.

Owing to the rapid development of the cosmetic industry, cosmetic safety has become the focus of consumers' attention. However, in order to achieve the desired effects in the short term, the illegal addition of hormones in cosmetics has emerged frequently, which could induce skin problems and even skin cancer after long-term use. Therefore, it is of great significance to master the illegal addition in cosmetics and effectively detect the hormones that may exist in cosmetics. In this review, we analyze the illegally added hormone types, detection values, and cosmetic types, as well as discuss the hormone risks in cosmetics for human beings, according to the data in unqualified cosmetics in China from 2017 to 2022. Results showed that although the frequency of adding hormones in cosmetics has declined, hormones are still the main prohibited substances in illegal cosmetics, especially facial masks. Because of the complex composition and the low concentration of hormones in cosmetics, it is necessary to combine efficient sample preparation technology with instrumental analysis. In order to give the readers a comprehensive overview of hormone analytical technologies in cosmetics, we summarize the advanced sample preparation techniques and commonly used detection techniques of hormones in cosmetics in the last decade (2012-2022). We found that ultrasound-assisted extraction, solid phase extraction, and microextraction coupled with chromatographic analysis are still the most widely used analytical technologies for hormones in cosmetics. Through the investigation of market status, the summary of sample pretreatment and detection technologies, as well as the discussion of their development trends in the future, our purpose is to provide a reference for the supervision of illegal hormone residues in cosmetics.

Plasma Exosomal AKR1C3 mRNA Expression Is a Predictive and Prognostic Biomarker in Patients with Metastatic Castration-Resistant Prostate Cancer.

PURPOSE: Aldo-keto reductase family 1 member C3 (AKR1C3) is important in prostate cancer progression, being a potential biomarker in metastatic castration-resistant prostate cancer (mCRPC). Previous explorations of AKR1C3 are mainly based on tissue samples. This study investigates using plasma-based liquid biopsy to validate the prognostic and predictive value of AKR1C3 in patients with mCRPC . MATERIALS AND METHODS: We prospectively recruited 62 patients with mCRPC. All patients received repeated prostate biopsies at the time of mCRPC diagnosis, and immunohistochemistry (IHC) staining was used to detect protein expression of AKR1C3 in the tissues. We took their blood simultaneously and performed digital droplet polymerase chain reaction (ddPCR) to measure expression levels of AKR1C3 in the exosomes. The detected plasma and tissue AKR1C3 expression levels were analyzed for patients' overall survival (OS) and progression-free survival under first-line abiraterone use (ABI-PFS). RESULTS: All other baseline characteristics were balanced between the 2 groups. 15/62 (24.2%) and 25/62 (40.3%) patients showed AKR1C3-EXO positive (≥20 copies/20 µL) and AKR1C3-IHC positive, respectively. Positive AKR1C3-EXO expression was associated with decreased patients' survival [ABI-PFS: 3.9 vs 10.1 months, P < .001; OS: 16.2 vs 32.5 months, P < .001]. AKR1C3-IHC positivity was also correlated with ABI-PFS and OS (P = .010, P = .016). In patients with worse baseline blood tests (including higher alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) level and lower hemoglobin (HB) level), and lower ISUP/WHO group (<4), their OS was significantly worse when showing AKR1C3-EXO positive. CONCLUSION: AKR1C3-EXO is associated with patient prognosis regarding OS and ABI-PFS and can be used as a biomarker in mCRPC.

Homologous recombination deficiency (HRD) score in aggressive prostatic adenocarcinoma with or without intraductal carcinoma of the prostate (IDC-P).

BACKGROUND: Intraductal carcinoma of the prostate (IDC-P) is a subtype of prostate cancer featured by poor prognosis. Previous studies suggested IDC-P could have a potentially unstable genome. Homologous recombination deficiency (HRD) score is a result-oriented method to describe the genomic instability status. This study investigates the association of HRD scores with IDC-P and other clinicopathological factors and the prognostic implication of HRD scores in an aggressive prostate cancer cohort. METHODS: This study involved 123 PCa patients, including high-risk localized (M0) and de novo metastatic (M1) diseases. HRD score is calculated based on over 10,000 single-nucleotide polymorphisms distributed across the human genome. We explored the association between HRD scores and clinicopathological characteristics, genomic alterations, and patients' prognoses using rank-sum tests, chi-square tests, Kaplan-Meier curves, and Cox proportional hazards method. RESULTS: The median HRD score of this cohort is 21.0, with 65 (52.8%) patients showing HRD score≥21. Tumors with IDC-P displayed higher HRD scores than adenocarcinoma (P=0.002); other high HRD score-related factors included M1 (P =0.008) and high ISUP grades (4-5) (P=0.001). MYC mutations were associated with high HRD scores (P<0.001) in the total cohort. TP53 mutations (P=0.010) and HRR pathway mutations (P=0.028) corresponded to high HRD scores in IDC-P positive and non-IDC-P patients, respectively, but not vice versa. HRD scores higher than 21 indicated significantly worse survival in the total cohort. CONCLUSIONS: M1, high Gleason score, and IDC-P pathology represent higher HRD scores in PCa. Tumors with IDC-P might have different driven mechanisms for high HRD scores than non-IDC-P. HRD score displayed prognostic value in this aggressive prostate cancer cohort.

A unified framework for packing deformable and non-deformable subcellular structures in crowded cryo-electron tomogram simulation.

BACKGROUND: Cryo-electron tomography is an important and powerful technique to explore the structure, abundance, and location of ultrastructure in a near-native state. It contains detailed information of all macromolecular complexes in a sample cell. However, due to the compact and crowded status, the missing edge effect, and low signal to noise ratio (SNR), it is extremely challenging to recover such information with existing image processing methods. Cryo-electron tomogram simulation is an effective solution to test and optimize the performance of the above image processing methods. The simulated images could be regarded as the labeled data which covers a wide range of macromolecular complexes and ultrastructure. To approximate the crowded cellular environment, it is very important to pack these heterogeneous structures as tightly as possible. Besides, simulating non-deformable and deformable components under a unified framework also need to be achieved. RESULT: In this paper, we proposed a unified framework for simulating crowded cryo-electron tomogram images including non-deformable macromolecular complexes and deformable ultrastructures. A macromolecule was approximated using multiple balls with fixed relative positions to reduce the vacuum volume. A ultrastructure, such as membrane and filament, was approximated using multiple balls with flexible relative positions so that this structure could deform under force field. In the experiment, 400 macromolecules of 20 representative types were packed into simulated cytoplasm by our framework, and numerical verification proved that our method has a smaller volume and higher compression ratio than the baseline single-ball model. We also packed filaments, membranes and macromolecules together, to obtain a simulated cryo-electron tomogram image with deformable structures. The simulated results are closer to the real Cryo-ET, making the analysis more difficult. The DOG particle picking method and the image segmentation method are tested on our simulation data, and the experimental results show that these methods still have much room for improvement. CONCLUSION: The proposed multi-ball model can achieve more crowded packaging results and contains richer elements with different properties to obtain more realistic cryo-electron tomogram simulation. This enables users to simulate cryo-electron tomogram images with non-deformable macromolecular complexes and deformable ultrastructures under a unified framework. To illustrate the advantages of our framework in improving the compression ratio, we calculated the volume of simulated macromolecular under our multi-ball method and traditional single-ball method. We also performed the packing experiment of filaments and membranes to demonstrate the simulation ability of deformable structures. Our method can be used to do a benchmark by generating large labeled cryo-ET dataset and evaluating existing image processing methods. Since the content of the simulated cryo-ET is more complex and crowded compared with previous ones, it will pose a greater challenge to existing image processing methods.

Recent Advances in Nanomaterial-Enabled Wearable Sensors: Material Synthesis, Sensor Design, and Personal Health Monitoring.

Wearable sensors have gained much attention due to their potential in personal health monitoring in a timely, cost-effective, easy-operating, and noninvasive way. In recent studies, nanomaterials have been employed in wearable sensors to improve the sensing performance in view of their excellent properties. Here, focus is mainly on the nanomaterial-enabled wearable sensors and their latest advances in personal health monitoring. Different kinds of nanomaterials used in wearable sensors, such as metal nanoparticles, carbon nanomaterials, metallic nanomaterials, hybrid nanocomposites, and bio-nanomaterials, are reviewed. Then, the progress of nanomaterial-based wearable sensors in personal health monitoring, including the detection of ions and molecules in body fluids and exhaled breath, physiological signals, and emotion parameters, is discussed. Furthermore, the future challenges and opportunities of nanomaterial-enabled wearable sensors are discussed.

Two-dimensional MXene nanosheets (types Ti3C2Tx and Ti2CTx) as new ion-to-electron transducers in solid-contact calcium ion-selective electrodes.

Two kinds of two-dimensional MXene (of type Ti3C2Tx and Ti2CTx) nanosheets are described for use in solid-contact ion-selective electrodes (SC-ISEs) where they act as ion-to-electron transducers. Electrochemical characterizations show that the MXene-coated electrodes possess high double layer capacitance and enable rapid electron transport. This demonstrates the enhanced efficiency of MXene-based solid-contact layers to improve ion-electron transduction. Both Ti3C2Tx- and Ti2CTx-based SC-ISEs exhibited a Nernstian response (26.4 and 24.9 mV/decade, respectively) between 10-1 and 10-5.5 M Ca(II) concentrations with rapid response (<10 s) and low limits of detection (0.79 µM and 1.0 µM, respectively). The SC-ISEs display a lower charge impedance compared to ISEs without solid-contact layer. The new SC-ISEs possess outstanding potentiometric performance, extraordinary long-term stability, and insensitivity to light, CO2, O2, and redox couples, thus showing great promising prospect for routine sensing applications. Graphical abstractSchematic representation of MXene nanosheets for use as new intermediate layers in solid-contact ion-selective electrodes (SC-ISEs) for the potentiometric detection of calcium ion.

A disposable electrochemical sensor based on electrospinning of molecularly imprinted nanohybrid films for highly sensitive determination of the organotin acaricide cyhexatin.

Nanofibrous polyporous membranes imprinted with cyhexatin (CYT) were formed via the ordered distribution of the imprints in electrospun nanofibers. The MIPs have a high mass transfer rate and enhanced adsorption capacity. In addition, a printed carbon electrode with enhanced sensitivity was developed via electrochemical fabrication of reduced graphene oxide (rGO) and gold nanoparticles (AuNPs). The molecularly imprinted sensor exhibits excellent selectivity and sensitivity for CYT. The structure and morphology of the nanohybrid films were characterized by using scanning electron microscopy, atomic force microscopy and chronoamperometry. The sensing performances were evaluated by cyclic voltammetry, differential pulse voltammetry and electrochemical impedance spectroscopy by using hexacyanoferrate(IV) as an electrochemical probe. The electrode, best operated at a working potential of around 0.16 V (vs. Ag/AgCl), has a linear response in the 1-800 ng mL-1 CYT concentration range and a detection limit of 0.17 ng mL-1 (at S/N = 3). The sensor demonstrated satisfactory recoveries when applied to the determination of CYT in spiked pear samples. Graphical abstract Schematic presentation of the electrochemical sensor for detection of CYT.

Metallic Transition Metal Dichalcogenide Nanosheets as an Effective and Biocompatible Transducer for Electrochemical Detection of Pesticide.

Owing to their large specific surface, favorable electrical conductivity, and excellent electrocatalytic capabilities, two-dimensional transition metal dichalcogenides have received considerable attention in the field of biosensors. On the basis of these properties, we developed a portable and disposable enzyme-based biosensor for paraoxon detection using a metallic MoS2 nanosheets modified screen-printed electrode (SPE). The exfoliated ultrathin metallic MoS2 nanosheets can accelerate the electron transfer on electrode surface and contribute to the immobilization of acetylcholinesterase (AChE) via the cross-linking of glutaraldehyde. Electrodeposited gold nanoparticles (AuNPs) on SPE were used to immobilize MoS2 nanosheets through the interaction between Au atoms on AuNPs and S atoms on MoS2. Using acetylcholine as the substrate, AChE can catalyze the formation of electroactive thiocholine and further generate the redox current. In the presence of paraoxon, the activity of AChE can be inhibited, making the related electrochemical signals weaken. Under the optimized conditions, this electrochemical biosensor exhibited a favorable linear relationship with the concentration of paraoxon from 1.0 to 1000 µg L-1, with the detection limit of 0.013 µg L-1. Furthermore, this developed biosensor was successfully applied to detect paraoxon in pretreated apple and pakchoi samples, which can provide a reliable method for the rapid analysis of organophosphorus pesticides in agricultural products.

A highly selective electrochemical sensor based on molecularly imprinted polypyrrole-modified gold electrode for the determination of glyphosate in cucumber and tap water.

An electrochemical sensor based on molecularly imprinted polypyrrole (MIPPy) was developed for selective and sensitive detection of the herbicide glyphosate (Gly) in cucumber and tap water samples. The sensor was prepared via synthesis of molecularly imprinted polymers on a gold electrode in the presence of Gly as the template molecule and pyrrole as the functional monomer by cyclic voltammetry (CV). The sensor preparation conditions including the ratio of template to functional monomers, number of CV cycles in the electropolymerization process, the method of template removal, incubation time, and pH were optimized. Under the optimal experimental conditions, the DPV peak currents of hexacyanoferrate/hexacyanoferrite changed linearly with Gly concentration in the range from 5 to 800 ng mL-1, with a detection limit of 0.27 ng mL-1 (S/N = 3). The sensor was used to detect the concentration of Gly in cucumber and tap water samples, with recoveries ranging from 72.70 to 98.96%. The proposed sensor showed excellent selectivity, good stability and reversibility, and could detect the Gly in real samples rapidly and sensitively. Graphical abstract Schematic illustration of the experimental procedure to detect Gly using the MIPPy electrode.

Prognostic significance of circulating tumor DNA in urothelial carcinoma: a systematic review and meta-analysis.

BACKGROUND: Circulating tumor DNA (ctDNA) has emerged as a noninvasive technique that provides valuable insights into molecular profiles and tumor disease management. This study aimed to evaluate the prognostic significance of circulating tumor DNA (ctDNA) in urothelial carcinoma (UC) through a systematic review and meta-analysis. METHODS: A comprehensive search was conducted in MEDLINE, EMBASE, and the Cochrane Library from the inception to December 2023. Studies investigating the prognostic value of ctDNA in UC were included. Hazard ratios (HRs) of disease-free survival (DFS) and overall survival (OS) were extracted. Overall meta-analysis and subgroup exploration stratified by metastatic status, ctDNA sampling time, treatment type, and detection method was performed using the R software (version 4.2.2). RESULTS: A total of 16 studies with 1725 patients were included. Fourteen studies assessed the association between baseline ctDNA status and patient outcomes. Patients with elevated ctDNA levels exhibited significantly worse DFS (HR=6.26; 95% CI: 3.71-10.58, P <0.001) and OS (HR=4.23; 95% CI: 2.72-6.57, P <0.001) regardless of metastatic status, ctDNA sampling time, treatment type, and detection methods. Six studies evaluated the prognostic value of ctDNA dynamics in UC. Patients who showed a decrease or clearance in ctDNA levels during treatment or observation demonstrated more favorable DFS (HR=0.26, 95% CI: 0.17-0.41, P <0.001) and OS (HR=0.21, 95% CI: 0.11-0.38, P <0.001) compared to those who did not. The association remained consistent across the subgroup analysis based on metastatic status and detection methods. In the immune checkpoint inhibitor-treated setting, both lower baseline ctDNA level and ctDNA decrease during the treatment were significantly associated with more favorable oncologic outcomes. Furthermore, specific gene mutations such as FGFR3 identified in ctDNA also demonstrated predictive value in UC patients. CONCLUSION: This meta-analysis demonstrates a strong association of ctDNA status and its dynamic change with survival outcomes in UC, suggesting substantial clinical utility of ctDNA testing in prognosis prediction and decision making in this setting.

Genomic and Evolutionary Characterization of Concurrent Intraductal Carcinoma and Adenocarcinoma of the Prostate.

Intraductal carcinoma of the prostate (IDC-P) is a lethal prostate cancer subtype that generally coexists with invasive high-grade prostate acinar adenocarcinoma (PAC) but exhibits distinct biological features compared with concomitant adenocarcinoma. In this study, we performed whole-exome, RNA, and DNA-methylation sequencing of IDC-P, concurrent invasive high-grade PAC lesions, and adjacent normal prostate tissues isolated from 22 radical prostatectomy specimens. Three evolutionary patterns of concurrent IDC-P and PAC were identified: early divergent, late divergent, and clonally distant. In contrast to those with a late divergent evolutionary pattern, tumors with clonally distant and early divergent evolutionary patterns showed higher genomic, epigenomic, transcriptional, and pathologic heterogeneity between IDC-P and PAC. Compared with coexisting PAC, IDC-P displayed increased expression of adverse prognosis-associated genes. Survival analysis based on an independent cohort of 505 patients with metastatic prostate cancer revealed that IDC-P carriers with lower risk International Society of Urological Pathology (ISUP) grade 1-4 adenocarcinoma displayed a castration-resistant free survival as poor as those with the highest risk ISUP grade 5 tumors that lacked concurrent IDC-P. Furthermore, IDC-P exhibited robust cell-cycle progression and androgen receptor activities, characterized by an enrichment of cellular proliferation-associated master regulators and genes involved in intratumoral androgen biosynthesis. Overall, this study provides a molecular groundwork for the aggressive behavior of IDC-P and could help identify potential strategies to improve treatment of IDC-P. SIGNIFICANCE: The genomic, transcriptomic, and epigenomic characterization of concurrent intraductal carcinoma and adenocarcinoma of the prostate deepens the biological understanding of this lethal disease and provides a genetic basis for developing targeted therapies.

Metabolome shifts triggered by chlorine sanitisation induce Escherichia coli on fresh produce into the viable but nonculturable state.

Facing the increasing occurrence of "big six" Escherichia coli outbreaks linked to fresh produce, chlorine-based sanitisers are widely used for fresh produce decontamination in recent years. However, latest finding that chlorine may induce E. coli cells into a viable not nonculturable (VBNC) state is bringing a new challenge to the fresh produce industry. VBNC cells are undetectable by the plate count test, and yet they retain pathogenicity and are more antibiotic-resistant than culturable cells. As a result, their eradication is critical to ensure the safety of fresh produce. Understanding VBNC cells at the metabolic level may provide a breakthrough for their eradication. Therefore, this study was carried out to collect the VBNC pathogenic E. coli (O26:H11, O121:H19, and O157:H7) cells from chlorine-treated pea sprouts and characterise them using NMR-based metabolomics. From the globally increased metabolite contents detected in the VBNC E. coli cells as compared to the culturable cells, mechanisms underlying E. coli's VBNC induction were elucidated. These include rendering the energy generation scheme to become more compatible with the lowered energy needs, disaggregating protein aggregates to release amino acids for osmoprotection and later resuscitation, as well as increasing cAMP content to downregulate RpoS. These identified metabolic characteristics can inspire future development of targeted measures for VBNC E. coli cell inhibition. Our methods can also be applied to other pathogens to help lower the risk of overall foodborne diseases.

A Colorimetric Sensor Enabled with Heterogeneous Nanozymes with Phosphatase-like Activity for the Residue Analysis of Methyl Parathion.

In this study, a colorimetric sensor was developed for the detection of organophosphorus pesticides (OPs) using a heterogeneous nanozyme with phosphatase-like activity. Herein, this heterogeneous nanozyme (Au-pCeO2) was obtained by the modification of gold nanoparticles on porous cerium oxide nanorods, resulting in synergistic hydrolysis performance for OPs. Taking methyl parathion (MP) as the target pesticide, the catalytic performance and mechanism of Au-pCeO2 were investigated. Based on the phosphatase-like Au-pCeO2, a dual-mode colorimetric sensor for MP was put forward by the analysis of the hydrolysis product via a UV-visible spectrophotometer and a smartphone. Under optimum conditions, this dual-mode strategy can be used for the on-site analysis of MP with concentrations of 5 to 200 µM. Additionally, it can be applied for MP detection in pear and lettuce samples with recoveries ranging from 85.27% to 115.87% and relative standard deviations (RSDs) not exceeding 6.20%, which can provide a simple and convenient method for OP detection in agricultural products.

Predictability and Utility of Contrast-Enhanced CT on Occult Lymph Node Metastasis for Patients with Clinical Stage IA-IIA Lung Adenocarcinoma: A Double-Center Study.

RATIONALE AND OBJECTIVES: With the advantage of minimizing damage and preserving more functional lung tissue, limited surgery is considered depend on the lymph node (LN) involvement situation. However, occult lymph node metastasis (OLM) may be ignored by limited surgery and become a risk factor for local recurrence after surgical resection. The aim of this study was to assess the risk factors for OLM based on computed tomography enhanced image in patients with clinical lung adenocarcinoma (ADC). MATERIALS AND METHODS: From January 2016 to July 2022, 707 patients with clinical stage IA-IIA ADC underwent lobectomy with systematic LN dissection and were divided into training and validation group based on different institution. Univariate analysis followed by multivariable logistic regression were performed to estimate different risk factors of OLM. A predictive model was established with visual nomogram and external validation, and evaluated in terms of accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve (AUC). RESULTS: Fifty-nine patients were diagnosed with OLM (11.9%), and four independent predictors of LN involvement were identified: larger consolidation diameter (odds ratio [OR], 2.35, 95% confidence interval [CI]: 1.06, 5.22, p = 0.013), bronchovascular bundle thickening (OR, 1.99, 95% CI: 1.00, 3.95, p = 0.049), lobulation (OR, 2.92, 95% CI: 1.22, 6.99, p = 0.016) and obstructive change (OR, 1.69, 95% CI: 1.17, 6.16, p = 0.020). The model showed good calibration (Hosmer-Lemeshow goodness-of-fit, p = 0.816) with an AUC of 0.821 (95% CI: 0.775, 0.853). For the validation group, the AUC was 0.788 (95% CI: 0.732, 0.806). CONCLUSION: Our predictive model can non-invasively assess the risk of OLM in patients with clinical stage IA-IIA ADC, enable surgeons perform an individualized prediction preoperatively, and assist the clinical decision-making procedure.

Electrochemical Sensor Based on Laser-Induced Graphene for Carbendazim Detection in Water.

Carbendazim (CBZ) abuse can lead to pesticide residues, which may threaten the environment and human health. In this paper, a portable three-electrode sensor based on laser-induced graphene (LIG) was proposed for the electrochemical detection of CBZ. Compared with the traditional preparation method of graphene, LIG is prepared by exposing the polyimide film to a laser, which is easily produced and patterned. To enhance the sensitivity, platinum nanoparticles (PtNPs) were electrodeposited on the surface of LIG. Under optimal conditions, our prepared sensor (LIG/Pt) has a good linear relationship with CBZ concentration in the range of 1-40 µM, with a low detection limit of 0.67 µM. Further, the sensor shows good recovery rates for the detection of CBZ in wastewater, which provides a fast and reliable method for real-time analysis of CBZ residues in water samples.

Research on the comparison of impact resistance characteristics between energy absorption and conventional hydraulic columns in fluid-solid coupling.

Rock burst disaster affects underground mining safety. The energy-absorbing hydraulic support for preventing tunnel impact has been implemented in rock burst mines. In order to compare the impact resistance characteristics of conventional columns and energy-absorbing columns, based on the derivation of energy theory, the CEL fluid-solid coupling simulation algorithm is used to simulate the process of static load 1000 kN superimposed impact load 1500 kN on φ180 mm type conventional column and energy-absorbing column. Combined with the static-dynamic combined test of the 6500 kN impact testing machine on the column, the accuracy and reliability of the CEL simulation column impact response are verified. The results showed that compared with conventional columns, the reaction force of energy-absorbing columns is reduced by 32.55%. The stress and expansion of the cylinder are significantly reduced. The acceleration of the mass movement has been reduced by 59.46%. The addition of the energy-absorbing device enhances the system's energy absorption by 33.46%, thereby reducing the energy absorption of the column itself to 23.58%. Additionally, the deformation of the energy-absorbing device increases the effective displacement by 239.45%. This also prolongs the impact duration, ensuring sufficient time for the safety valve to open, safeguarding the support from damage, and enhancing the overall integrity of the tunnel.

The therapeutic efficacy of radical prostatectomy and external beam radiation therapy in patients with different pathological patterns of prostate cancer.

BACKGROUND: We aim to investigate the prognostic value of different pathological patterns of non-adenocarcinoma prostate cancers (PCa) in radical prostatectomy (RP) and external beam radiation therapy (EBRT). METHODS: Data of 470,258 localized PCa patients between 2004 and 2016 were collected from the Surveillance, Epidemiology, and End Results database. Propensity score matching was performed to balance the baseline characteristics of patients in different groups. Kaplan-Meier curves and Cox regression were used for survival analysis. Overall survival (OS) and cancer-specific survival (CSS) were set as endpoints. RESULTS: Totally, 1044 patients with non-adenocarcinoma patterns of PCa were included. Patients with small cell neuroendocrine carcinoma (SCNC) and neuroendocrine differentiation (NED) harbored the worst prognosis in both RP and EBRT among all pathological groups. RP exhibited superior effects to EBRT for this group of cases. Ductal carcinoma (DA) was also related to poorer survival outcomes versus PAC in both local therapies. Yet, for men with DA, both RP and EBRT still improved patients' prognosis against no local therapy (NLT), with RP being the superior modality. Cases harboring mucinous adenocarcinoma (MA) and signet ring cell carcinoma (SRCC) shared comparable clinical outcomes to men with PAC. However, for cases with MA, neither RP nor EBRT was related to better survival outcomes against NLT, while for patients with SRCC, both RP and EBRT prolonged patients' survival with similar effects. CONCLUSIONS: Our study provided a comprehensive view of the treatment effect of RP and EBRT in non-adenocarcinoma PCa patients. These findings could facilitate clinicians in making therapeutic decision-making for non-adenocarcinoma patients.

The prognostic value of the pretreatment lung immune prognostic index in patients with metastatic hormone-sensitive and castration-resistant prostate cancer.

Background: The lung immune prognostic index (LIPI) was first reported to predict the effectiveness of immune checkpoint inhibitors in patients with metastatic non-small cell lung cancer and there are no studies investigating the predictive value of LIPI for patients with PCa. This study explores the prognostic value of the LIPI in patients with metastatic hormone-sensitive prostate cancer (mHSPC) and metastatic castration-resistant prostate cancer (mCRPC). Methods: Data from 502 patients with mHSPC primarily treated with maximal androgen blockade (MAB; 89% of patients received MAB) and 158 patients with mCRPC who received abiraterone were retrospectively analyzed. All cases were classified into LIPI-good, LIPI-intermediate, and LIPI-poor groups based on their LIPI score as calculated with the derived neutrophil-to-lymphocyte ratio and lactate dehydrogenase level. The potential for LIPI to be used in predicting mCRPC-free survival (CFS), prostate-specific antigen (PSA) response, PSA-progression-free survival (PSA-PFS), and overall survival (OS) was analyzed. A propensity score matching (PSM) methodology was performed to balance the baseline factors of the different groups. Results: In the mHSPC cohort, patients of the LIPI-good (mCFS: 25.7 months; mOS: 93.3 months), LIPI-intermediate (mCFS: 14.8 months; mOS: 51.9 months), and LIPI-poor group (mCFS: 6.8 months; mOS: 18.5 months) had sequentially worse clinical outcomes (P<0.001 for all pairwise comparisons). The results remained consistent after PSM. Multivariate Cox regression further confirmed that LIPI was an independent predictor of survival outcomes. Subgroup analysis verified that LIPI was associated with an unfavorable prognosis in all subgroups except for cases with visceral metastases or those receiving abiraterone or docetaxel. As for patients with mCRPC receiving abiraterone, LIPI was also an indicator of poor prognosis. Specifically, cases in the LIPI-good, LIPI-intermediate, and LIPI-poor groups had a ladder-shaped worse PSA response [71.4% (50/70) vs. 56.5% (39/69) vs. 36.8% (7/19); P=0.015], PSA-PFS (14.9 vs. 9.3 vs. 3.1 months; P<0.001), and OS (14.6 vs. 32.3 vs. 53.4 months; P<0.001). The results were robust even after PSM. Multivariate Cox regression confirmed that LIPI was an independent prognosticator of PSA-PFS and OS in patients with mCRPC treated with abiraterone. Conclusions: This study demonstrated that the baseline LIPI was a significant prognostic biomarker for patients with both mHSPC and mCRPC and could potentially facilitate risk classification and clinical decision-making.